Hostname: page-component-77c89778f8-rkxrd Total loading time: 0 Render date: 2024-07-18T12:49:51.714Z Has data issue: false hasContentIssue false

Progress in Clinical Neurosciences: Pharmacotherapies for the Secondar Prevention of Stroke

Published online by Cambridge University Press:  02 December 2014

Daniel G. Hackam
Affiliation:
Division of Clinical Pharmacology, University of Toronto, Institute for Clinical Evaluative Sciences, Toronto and the Sunnybrook & Women's College Hospital, Toronto, Ontario, Canada
Moira K. Kapral
Affiliation:
Department of Medicine, University of Toronto, Institute for Clinical Evaluative Sciences, Toronto and the Division of General Internal Medicine and Clinical Epidemiology, University Health Network, Toronto, Ontario, Canada
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Stroke is a leading cause of mortality and long-term disability worldwide. Survivors of a previous stroke or transient ischemic attack are vulnerable to further cerebrovascular events, as well as myocardial infarction, peripheral vascular disease, congestive heart failure and vascular death. Traditional approaches to the secondary prevention of stroke have included aspirin after ischemic stroke, warfarin for stroke associated with cardioembolic sources, and carotid endarterectomy for eligible candidates with significant carotid artery stenosis. In recent years, much evidence has emerged to support a broader array of pharmacotherapies, including newer antiplatelet agents, lipid lowering drugs, and several classes of blood pressure lowering therapies. Also under study are B vitamins for patients with cerebrovascular disease and hyper-homocysteinemia, and oral direct thrombin inhibitors for high-risk patients with atrial fibrillation. We review the literature to determine the clinical significance of these therapies, and provide recommendations regarding their use in the prevention of recurrent stroke.

Type
Review Article
Copyright
Copyright © The Canadian Journal of Neurological 2004

References

1.Hauptmann, J.Pharmacokinetics of an emerging new class of anticoagulant/antithrombotic drugs. A review of small-molecule thrombin inhibitors. Eur J Clin Pharmacol 2002; 57(11):751758.CrossRefGoogle ScholarPubMed
2.Halperin, JL.SPORTIF III: A Long-Term Randomized Trial Comparing Ximelagatran with Warfarin for Prevention of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation. American College of Cardiology Annual Scientific Session. Late Breaking Clinical Trials III. Chicago, Illinois, USA. 4-1-2003.Google Scholar
3.Halperin, JL.Efficacy and Safety Study of Oral Direct Thrombin Inhibitor Ximelagatran Compared with Dose-Adjusted Warfarin in the Prevention of Stroke and Systemic Embolic Events in Patients with Atrial Fibrillation (SPORTIF V). American Heart Association Scientific Sessions. Plenary Session VII: Late-Breaking Clinical Trials. Orlando, Florida, USA. 2003.Google Scholar
4.Byington, RP, Davis, BR, Plehn, JF, et al.Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project. Circulation 2001; 103(3):387392.CrossRefGoogle ScholarPubMed
5.Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344(8934):13831389.Google Scholar
6.Plehn, JF, Davis, BR, Sacks, FM, et al.Reduction of stroke incidence after myocardial infarction with pravastatin: the Cholesterol and Recurrent Events (CARE) study. The Care Investigators. Circulation 1999; 99(2):216223.CrossRefGoogle Scholar
7.Schwartz, GG, Olsson, AG, Ezekowitz, MD, et al.Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001; 285(13):17111718.CrossRefGoogle ScholarPubMed
8.White, HD, Simes, RJ, Anderson, NE, et al.Pravastatin therapy and the risk of stroke. N Engl J Med 2000; 343(5):317326.CrossRefGoogle ScholarPubMed
9.Corvol, JC, Bouzamondo, A, Sirol, M, et al.Differential effects of lipid-lowering therapies on stroke prevention: a meta-analysis of randomized trials. Arch Intern Med 2003; 163(6):669676.CrossRefGoogle ScholarPubMed
10.Crouse, JR III,Byington, RP, Hoen, HM, Furberg, CD.Reductase inhibitor monotherapy and stroke prevention. Arch Intern Med 1997; 157(12):13051310.CrossRefGoogle ScholarPubMed
11.Ross, SD, Allen, IE, Connelly, JE, et al.Clinical outcomes in statin treatment trials: a meta-analysis. Arch Intern Med 1999; 159(15):17931802.CrossRefGoogle ScholarPubMed
12.Warshafsky, S, Packard, D, Marks, SJ, et al.Efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for prevention of stroke. J Gen Intern Med 1999; 14(12):763774.CrossRefGoogle Scholar
13.Liao, JK.Beyond lipid lowering: the role of statins in vascular protection. Int J Cardiol 2002; 86(1):518.CrossRefGoogle ScholarPubMed
14.Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360(9326):722.CrossRefGoogle Scholar
15.Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 285(19):24862497.CrossRefGoogle Scholar
16.Amarenco, P, Bogousslavsky, J, Callahan, AS, et al.Design and baseline characteristics of the stroke prevention by aggressive reduction in cholesterol levels (SPARCL) study. Cerebrovasc Dis 2003; 16(4):389395.Google ScholarPubMed
17.Wood, D, De Backer, G, Faergeman, O, et al.Prevention of coronary heart disease in clinical practice. Summary of recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. J Hypertens 1998; 16(10):14071414.CrossRefGoogle ScholarPubMed
18.Rodriguez, BL, D’Agostino, R, Abbott, RD, et al.Risk of hospitalized stroke in men enrolled in the Honolulu Heart Program and the Framingham Study: a comparison of incidence and risk factor effects. Stroke 2002; 33(1):230236.CrossRefGoogle ScholarPubMed
19.Sacco, RL, Wolf, PA, Kannel, WB, McNamara, PM.Survival and recurrence following stroke. The Framingham study. Stroke 1982; 13(3):290295.CrossRefGoogle ScholarPubMed
20.Straus, SEM, Majumdar, SRM, McAlister, FAM.New Evidence for Stroke Prevention: Scientific Review. JAMA2002; 288(11):13881395.Google Scholar
21.Schrader, J, Luders, S, Kulschewski, A, et al.The ACCESS Study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors. Stroke 2003; 34(7):16991703.CrossRefGoogle ScholarPubMed
22.Lewington, S, Clarke, R, Qizilbash, N, Peto, R, Collins, R.Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360(9349):19031913.Google ScholarPubMed
23.Rodgers, A, MacMahon, S, Gamble, G, et al.Blood pressure and risk of stroke in patients with cerebrovascular disease. Br Med J 1996; 313(7050):147.CrossRefGoogle ScholarPubMed
24.Progressive Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358(9287):10331041.CrossRefGoogle Scholar
25.Sleight, P, Yusuf, S, Pogue, J, et al.Blood-pressure reduction and cardiovascular risk in HOPE study. Lancet 2001; 358(9299):21302131.CrossRefGoogle ScholarPubMed
26.MacMahon, S, Peto, R, Cutler, J, et al.Blood pressure, stroke, and coronary heart disease. Part 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990; 335(8692):765774.CrossRefGoogle ScholarPubMed
27.PATS Collaborating Group. Post-stroke antihypertensive treatment study. A preliminary result. Chin Med J 1995; 108(9):710717.Google Scholar
28.Gueyffier, F, Boissel, JP, Boutitie, F, et al.Effect of antihypertensive treatment in patients having already suffered from stroke : gathering the evidence. Stroke 1997; 28(12):2557.CrossRefGoogle ScholarPubMed
29.The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002; 288(23):29812997.CrossRefGoogle Scholar
30.Wing, LMH, Reid, CM, Ryan, P, et al.A Comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 2003; 348(7):583592.CrossRefGoogle ScholarPubMed
31.Baker, EH, Duggal, A, Dong, Y, et al.Amiloride, a specific drug for hypertension in black people with T594M variant? Hypertension 2002; 40(1):1317.CrossRefGoogle ScholarPubMed
32.Spence, JD.Physiologic tailoring of therapy for resistant hypertension: 20 years’ experience with stimulated renin profiling. Am J Hypertens 1999; 12(11 Pt 1):10771083.CrossRefGoogle ScholarPubMed
33.The Dutch TIA Trial Study Group. Trial of secondary prevention with atenolol after transient ischemic attack or nondisabling ischemic stroke. Stroke 1993; 24(4):543548.CrossRefGoogle Scholar
34.Messerli, FH, Grossman, E, Goldbourt, U.Are {beta}-blockers efficacious as first-line therapy for hypertension in the elderly? A systematic review. JAMA 1998; 279(23):19031907.CrossRefGoogle ScholarPubMed
35.Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Lancet 2000; 356(9246):19551964.CrossRefGoogle Scholar
36.Mangoni, AA, Jackson, SH.Homocysteine and cardiovascular disease: current evidence and future prospects. Am J Med 2002; 112(7):556565.CrossRefGoogle ScholarPubMed
37.Wald, DS, Law, M, Morris, JK.Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. Br Med J 2002; 325(7374):1202.CrossRefGoogle ScholarPubMed
38.Hackam, DG, Peterson, JC, Spence, JD.What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 micromol/L. Am J Hypertens 2000; 13(1 Pt 1):105110.CrossRefGoogle Scholar
39.Homocysteine Lowering Trialists’ Collaboration. Lowering blood homocysteine with folic acid-based supplements: meta-analysis of randomised trials. Indian Heart J 2000; 52(7 Suppl):S59S64.Google Scholar
40.Spence, JD, Howard, VJ, Chambless, LE, et al.Vitamin Intervention for Stroke Prevention (VISP) trial: rationale and design. Neuroepidemiology 2001; 20(1):1625.Google ScholarPubMed
41.VITATOPS Trial Study Group. The VITATOPS (Vitamins to Prevent Stroke) Trial: rationale and design of an international, large, simple, randomised trial of homocysteine-lowering multivitamin therapy in patients with recent transient ischaemic attack or stroke. Cerebrovasc Dis 2002; 13(2):120126.CrossRefGoogle Scholar
42.Lange, HW, Dambrink, J-H, Pasalary, M, et al.Folate Therapy Increases In-Stent Restenosis: Results From the Folate After Coronary Intervention Trial (FACIT). American College of Cardiology 52nd Annual Scientific Meeting March 30, 2003 Chicago, Illinois 2003.Google Scholar
43.Schnyder, G, Roffi, M, Flammer, Y, Pin, R, Hess, OM.Effect of homocysteine-lowering therapy with folic acid, vitamin B(12), and vitamin B(6) on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA 2002; 288(8):973979.CrossRefGoogle Scholar
44.Hankey, GJ, Jamrozik, K, Broadhurst, RJ, et al.Long-term risk of first recurrent stroke in the Perth Community Stroke Study. Stroke 1998; 29(12):24912500.CrossRefGoogle ScholarPubMed
45.Wilterdink, JL, Easton, JD.Vascular event rates in patients with atherosclerotic cerebrovascular disease. Arch Neurol 1992; 49(8):857.CrossRefGoogle ScholarPubMed
46.Bravata, DM, Ho, SY, Brass, LM, et al.Long-term mortality in cerebrovascular disease. Stroke 2003; 34(3):699704.CrossRefGoogle ScholarPubMed
47.Wolf, PA, Clagett, GP, Easton, JD, et al.Preventing ischemic stroke in patients with prior stroke and transient ischemic attack : a statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke 1999; 30(9):19911994.CrossRefGoogle ScholarPubMed
48.Gorelick, PB.Stroke prevention therapy beyond antithrombotics: unifying mechanisms in ischemic stroke pathogenesis and implications for therapy: an invited review. Stroke 2002; 33(3):862875.CrossRefGoogle ScholarPubMed
49.Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324(7329):7186.CrossRefGoogle Scholar
50.Liem, A, Reynierse-Buitenwerf, GH, Zwinderman, AH, Jukema, JW, van Veldhuisen, DJ.Secondary prevention with folic acid: effects on clinical outcomes. J Am Coll Cardiol 2003; 41(12):21052113.CrossRefGoogle ScholarPubMed
51.Acheson, J, Danta, G, Hutchinson, EC.Controlled trial of dipyridamole in cerebral vascular disease. Br Med J 1969; 1(644):614615.CrossRefGoogle ScholarPubMed
52.Hypertension-Stroke Cooperative Study Group. Effect of antihypertensive treatment on stroke recurrence. JAMA 1974; 229(4):409418.CrossRefGoogle Scholar
53.Leren, P.The Oslo diet-heart study. Eleven-year report. Circulation 1970; 42(5):935942.CrossRefGoogle ScholarPubMed
54.Hankey, GJ.Stroke: How Large a Public Health Problem, and How Can the Neurologist Help? Arch Neurol 1999; 56(6):748.CrossRefGoogle Scholar
55.Taylor, AJ, Kent, SM, Flaherty, PJ, et al.ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness. Circulation 2002; 106(16):20552060.CrossRefGoogle ScholarPubMed
56.Knatterud, GL, Rosenberg, Y, Campeau, L, et al.Long-term effects on clinical outcomes of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation in the Post Coronary Artery Bypass Graft Trial. Circulation 2000; 102(2):157.CrossRefGoogle ScholarPubMed
57.Steinhubl, SR, Berger, PB, Mann, JT, III, et al.Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002; 288(19):24112420.CrossRefGoogle ScholarPubMed
58.Yusuf, S, Zhao, F, Mehta, SR, et al.Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345(7):494502.Google ScholarPubMed
59.The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157(21):24132446.CrossRefGoogle Scholar
60.Rothwell, PM, Howard, SC, Spence, JD.Relationship between blood pressure and stroke risk in patients with symptomatic carotid occlusive disease. Stroke 2003; 34(11):25832590.CrossRefGoogle ScholarPubMed
61.Yusuf, S.Two decades of progress in preventing vascular disease. Lancet 2002; 360(9326):23.CrossRefGoogle ScholarPubMed
62.Holloway, RGM, Benesch, CM, Rush, SRM.Stroke prevention: narrowing the evidence-practice gap. Neurology 2000; 54(10):18991906.CrossRefGoogle ScholarPubMed
63.Hillen, T, Dundas, R, Lawrence, E, et al.Antithrombotic and antihypertensive management 3 months after ischemic stroke : a prospective study in an inner city population. Stroke 2000; 31(2):469475.CrossRefGoogle Scholar
64.World Health Organization. The World Health Report 2002. Available at: http://www/who/int/whr/en/. Accessibility confirmed Jan 28, 2004.Google Scholar
65.Yusuf, S, Reddy, S, Ounpuu, S, Anand, S.Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 2001; 104(22):27462753.CrossRefGoogle ScholarPubMed
66.European Atrial Fibrillation Trial Study Group. Secondary prevention in nonrheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993; 320;342(8882):12551262.Google Scholar
67.Hart, RG, Benavente, O, McBride, R, Pearce, LA.Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999; 131(7):492501.CrossRefGoogle ScholarPubMed
68.Rothwell, PM, Eliasziw, M, Gutnikov, SA, et al.Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis. Lancet 2003; 361(9352):107116.CrossRefGoogle ScholarPubMed
69.Olsson, SB.Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with nonvalvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003; 362(9397):16911698.Google ScholarPubMed
70.Lalouschek, W, Lang, W, Mullner, M.Current strategies of secondary prevention after a cerebrovascular event: the Vienna stroke registry. Stroke 2001; 32(12):28602866.CrossRefGoogle ScholarPubMed
71.Hankey, GJ, Warlow, CP.Treatment and secondary prevention of stroke: evidence, costs, and effects on individuals and populations. Lancet 1999; 354(9188):14571463.CrossRefGoogle ScholarPubMed
72.Yusuf, S, Sleight, P, Pogue, J, et al.Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342(3):145153.Google Scholar
73.Turnbull, F.Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet 2003; 362(9395):15271535.Google ScholarPubMed
74.Tzourio, C, Anderson, C, Chapman, N, et al.Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med 2003; 163(9):10691075.Google Scholar
75.Dahlof, B, Devereux, RB, Kjeldsen, SE, et al.Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359(9311):9951003.CrossRefGoogle ScholarPubMed
76.Lithell, H, Hansson, L, Skoog, I, et al.The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. J Hypertens 2003; 21(5):875886.CrossRefGoogle Scholar
77.Eikelboom, JW, Hirsh, J, Weitz, JI, et al.Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105(14):16501655.CrossRefGoogle ScholarPubMed
78.Sandercock, P, Mielke, O, Liu, M, Counsell, C.Anticoagulants for preventing recurrence following presumed noncardioembolic ischaemic stroke or transient ischaemic attack. Cochrane Database Syst Rev 2003;(1):CD000248.Google ScholarPubMed
79.Algra, A, De Schryver, EL, van Gijn, J, Kappelle, LJ, Koudstaal, PJ.Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischemic attack or minor stroke of presumed arterial origin. Stroke 2003; 34(1):234235.CrossRefGoogle ScholarPubMed
80.Hackam, D, Anand, SS, Yusuf, S.Oral anticoagulant therapy in patients with coronary artery disease. Seminars in Vascular Medicine 2003; 3(3):323332.Google ScholarPubMed
81.Cohen, N, Almoznino-Sarafian, D, Alon, I, et al.Warfarin for stroke prevention still underused in atrial fibrillation: patterns of Omission. Stroke 2000; 31(6):12171222.CrossRefGoogle ScholarPubMed
82.Connolly, SJ.Preventing stroke in patients with atrial fibrillation: current treatments and new concepts. Am Heart J 2003; 145(3):418423.CrossRefGoogle ScholarPubMed
83.Grundmann, K, Jaschonek, K, Kleine, B, Dichgans, J, Topka, H.Aspirin nonresponder status in patients with recurrent cerebral ischemic attacks. J Neurol 2003; 250(1):6366.CrossRefGoogle ScholarPubMed
84.Gum, PA, Kottke-Marchant, K, Welsh, PA, White, J, Topol, EJ.A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003; 41(6):961965.CrossRefGoogle ScholarPubMed
85.De Schryver, EL, Algra, A, van Gijn, J.Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. Cochrane Database Syst Rev 2003;(1):CD001820.Google ScholarPubMed
86.Diener, HC, Cunha, L, Forbes, C, et al.European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996; 143(1-2):113.CrossRefGoogle ScholarPubMed
87.De Schryver, EL.Design of ESPRIT: an international randomized trial for secondary prevention after nondisabling cerebral ischaemia of arterial origin. European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) group. Cerebrovasc Dis 2000; 10(2):147150.CrossRefGoogle ScholarPubMed
88.Prevention Regimen For Effectively avoiding Second Strokes. Available at: http://www.strokecenter.org/trials 2003.Google Scholar
89.Hankey, G, Sudlow, C, Dunbabin, D.Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database of Systematic Reviews 2003; 1, 2003.Google Scholar
90.Paradiso-Hardy, FL, Angelo, CM, Lanctot, KL, Cohen, EA.Hematologic dyscrasia associated with ticlopidine therapy: evidence for causality. Can Med Assoc J 2000; 163(11):14411448.Google ScholarPubMed
91.Pitt, B, Waters, D, Brown, WV, et al.Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators. N Engl J Med 1999; 341(2):7076.CrossRefGoogle ScholarPubMed
92.Athyros, VG, Papageorgiou, AA, Mercouris, BR, et al.Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Curr Med Res Opin 2002; 18(4):220228.CrossRefGoogle Scholar
93.Mehler, PS, Coll, JR, Estacio, R, et al.Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes. Circulation 2003; 107(5):753756.CrossRefGoogle ScholarPubMed
94.Progressive Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet 2001; 358(9287):10331041.CrossRefGoogle Scholar
95.Neal, B, MacMahon, S, Chapman, N.Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2000; 356(9246):19551964.Google ScholarPubMed
96.Hansson, L, Zanchetti, A, Carruthers, SG, et al.Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351(9118):17551762.CrossRefGoogle ScholarPubMed
97.Zanchetti, A, Ruilope, LM.Antihypertensive treatment in patients with type-2 diabetes mellitus: what guidance from recent controlled randomized trials? J Hypertens 2002; 20(11):20992110.CrossRefGoogle ScholarPubMed
98.Tu, JV, Gong, Y.Trends in treatment and outcomes for acute stroke patients in Ontario, 1992-1998. Arch Intern Med 2003; 163(3):293297.CrossRefGoogle ScholarPubMed
99.Lalouschek, W, Lang, W, Greisenegger, S, Mullner, M.Determination of lipid profiles and use of statins in patients with ischemic stroke or transient ischemic attack. Stroke 2003; 34(1):105110.CrossRefGoogle ScholarPubMed
100.Kernan, WN, Viscoli, CM, Brass, LM, et al.Blood pressure exceeding national guidelines among women after stroke. Stroke 2000; 31(2):415419.CrossRefGoogle ScholarPubMed
101.CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996; 348(9038):13291339.CrossRefGoogle Scholar
102.Psaty, BM, Lumley, T, Furberg, CD, et al.Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis. JAMA 2003; 289(19):25342544.CrossRefGoogle ScholarPubMed
103.Staessen, JA, Wang, JG, Thijs, L.Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003. J Hypertens 2003; 21(6):10551076.CrossRefGoogle ScholarPubMed
104.Forette, F, Seux, ML, Staessen, JA, et al.The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002; 162(18):20462052.CrossRefGoogle ScholarPubMed
105.Forette, F, Seux, ML, Staessen, JA, et al.Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998; 352(9137):13471351.CrossRefGoogle ScholarPubMed
106.Mann, J, Julius, S.The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of cardiovascular events in hypertension. Rationale and design. Blood Press 1998; 7(3):176183.Google ScholarPubMed
107.Sever, PS, Dahlof, B, Poulter, NR, et al.Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators. J Hypertens 2001; 19(6):11391147.CrossRefGoogle ScholarPubMed